The long-term objective of this research is to determine the membrane mechanisms underlying the long-lasting changes in the basolateral amygdala (BLA) resulting from kindling-induced epileptogenesis, a model of human limbic epilepsy. In the amygdala, kindling results in enhanced glutamatergic transmission recorded electrophysiologically. Biochemical studies have shown that no significant changes occur in the number or function of inotropic glutamate receptors in the amygdala. In contrast, kindling induces an increase in phosphoinositol hydrolysis activated by metabotropic glutamate receptors, an effect that is long- lasting in the amygdala. Preliminary electrophysiological data also suggest changes in the function of metabotropic receptors. This study will test the hypothesis that kindling enhances membrane responses to activation of metabotropic glutamate receptors in a long-lasting and differential manner in the basolateral amygdala. Intracellular measurements using current and single electrode voltage clamp recording modes will be obtained in brain slice preparations from control animals and from animals kindled in vivo. The following specific aims will be addressed: 1) analyze the effects of the specific metabotropic glutamate receptor agonist, 1S, 3R-ACPD, on the electrophysiological properties of BLA neurons and determine the mechanism of action on specific membrane currents underlying the action of ACPD in control neurons, 2) analyze the long-lasting changes in ACPD actions in neurons from animals kindled in vivo, 3) determine the long-lasting changes in presynaptic action of metabotropic agonists on synaptic transmission in kindled neurons, 4) correlate cell morphology with long-lasting changes in responses to metabotropic receptor agonists and 5) analyze the membrane mechanisms underlying the APV- and CNQX- resistant EPSP recorded in kindled neurons. Information derived from the proposed studies will provide insight into the basic membrane mechanisms underlying epileptogenesis. Furthermore, understanding metabotropic glutamate receptor function in epileptic neurons may provide the basis of a new therapeutic approach to the treatment of epilepsy.